Sudden Hearing Loss a Risk for People Taking Phosphodiesterase-5 Inhibitors

Although the study found an association between hearing impairment and all PDE-5 inhibitor agents, the only significant association was with the use of sildenafil (OR of 2.05, 95% CI, 1.23-3.43). For the other agents, there was an elevated, albeit nonstatistical, association between tadalafil use and hearing impairment (OR 1.40, 95% CI, 0.49-4.04), and a weaker association with vardenafil (OR 0.88, 95% CI, 0.35-2.22).

According to the author of the study, Gerald McGwin, Jr., MS, PhD, a professor and vice chair in the department of epidemiology in the School of Public Health at the University of Alabama, Birmingham, the study was not able to tease out why sildenafil had the strongest association with hearing impairment, but he added that one possibility was that there were more people using sildenafil. In the study, sildenafil was the most widely used agent (80.3%), followed by vardenafil (20.2%) and tadalafil (12.8%).

He emphasized that the findings of the study need to be placed within the context of the limitations common to all epidemiologic studies. Along with the retrospective nature of the study and the potential for bias with self-reporting, he said that the type of hearing loss associated with the PDE-5 inhibitors (i.e., sudden hearing loss) is relatively uncommon. “You have a sort of needle-in-the-haystack situation,” he said. “You need a large epidemiologic study just to detect what may be a small effect.”

That said, he believes the findings of his study support the FDA warnings. “I think that the FDA warnings are reasonable absent more information,” he said. “There is a risk of some hearing loss and, until there is more epidemiologic data, that warning is warranted.”

In the most recent study, published in 2013, researchers retrospectively reviewed data on side effects of PDE-5 inhibitors from published studies and pharmacovigilance agencies in a number of countries (Laryngoscope. 2011;121:1049-1054). The study found 47 cases of sensorineural hearing loss related to PDE-5 inhibitor use reported in the published literature (n=4) and from pharmacovigilance agencies (n=43). Half of the cases reported were associated with use of sildenafil.

According to the authors, however, the number of cases in their review probably does not reflect the real number of cases of hearing loss related to PDE-5 inhibitors. They mention the potential for an additional 240 cases from clinical and recent FDA reports of adverse events that they were not able to confirm because of incomplete data and case histories. They also note the large variation among the pharmacovigilance agencies they contacted with regard to the level of detail and format of individual adverse event reports, as well as the overall poor response rate from national pharmacovigilance agencies and transnational organizations.